Chitosan derivative, sequestering agents for heavy metals

ABSTRACT

Chitosan derivatives formed by acylation of chitosan with a saturated or unsaturated organic diacid anhydride are employed as a skin moisturizing agent in a cosmetic composition comprising an aqueous solution containing 0.1-20 percent by weight of said chitosan derivative.

This is a division, of application Ser. No. 504,953 filed Sept. 11, 1974 now U.S. Pat. No. 3,953,608 which is a division of Ser. No. 251,263 filed May 8, 1972, now U.S. Pat. No. 3,879,376.

The present invention relates to novel macromolecular compounds derived from chitosan which present particularly advantageous properties as filmogens, as sequestrants of ions of heavy metals such as iron and copper and as skin moisturizing agent for incorporation into cosmetic compositions.

Chitosan is a product of the deacetylation of chitin, a natural polyglucosamine whose amine groups are acetylated and which is found in certain mushrooms and the shells of crustacea.

Since deacetylation of chitin by alkaline reagents cannot be performed completely, chitosan, which serves as the starting product for compounds of the invention, comprises in its molecule both free amine residues and acetylamine residues. The degree of deacetylation of chitin is evaluated by determining by titration the percentage of free base of the molecule, which is generally located below 95%.

Chitosan is, by the presence of these free amine groups, a cationic polymer, which presents the major drawback of being insoluble in an alkaline medium.

Known derivatives of chitosan, obtained by alkylation of this compound, hardly differ from chitosan itself as far as their alkaline solubility is concerned.

To improve this property of chitosan, the applicants have tried to make its molecule undergo other modifications. The difficulties encountered in these attempts are explained principally by the fact that chitosan is soluble only in an acid medium, in the form of salts. Further, it is known that it is generally very difficult to achieve condensation or addition reactions on amine salts. The applicants have now developed a process which makes it possible to acylate chitosan. Thus, the present invention relates to chitosan derivatives obtained by the acylation of this compound by means of saturated or unsaturated organic diacid anhydrides, followed if desired in the case of unsaturated anhydrides, by the addition on the double bonds of compounds with primary or secondary amine groups to provide other functional substituents.

The novel compounds according to the invention are polymers having monomer patterns of the formula ##STR1## scattered randomly in the molecule of the polymer, the numerical proportions of these three patterns being respectively 5 to 30% for A, 5 to 40% for B and 30 to 90% for C.

In formula C, R represents a member selected from the group consisting of the formula ##STR2## wherein R₁ is selected from the group consisting of hydrogen and methyl and n is equal to (a) O, in which case R₂, R₃ and R₄ each independently represent a member selected from the group consisting of hydrogen; methyl; hydroxyl; acetoxy; amino; monoalkylamino wherein the alkyl moiety has 1 to 12 carbon atoms or dialkylamino wherein the alkyl moiety has 1 to 3 carbon atoms, said monoalkylamino and dialkylamino being optionally substituted by one or more amine, hydroxyl, mercapto, carboxyl, alkylthio wherein the alkyl moiety has 1 to 8 carbon atoms or sulfonic groups; alkylthio wherein the alkyl moiety has 1 to 4 carbon atoms and carries an amine residue; and a residue of an oligopeptide such as glutathion or a product of protein hydrolysis, one at least of radicals R₂, R₃ and R₄ being a hydrogen atom and radicals R₂ and R₃ being able, in addition, to form together a methylene radical; and to (b) 1, in which case R₂, R₃ and R₄ each represent hydrogen.

The acid and base groups which appear in the molecules of the polymers according to the invention are able to be ionized in an aqueous solution, thus yielding salts either between two patterns B and C, or in the same pattern C.

These same ionized forms also appear in the presence of inorganic or organic bases and acids. The salts formed with these acids or bases are, of course, also a part of the invention.

These salts can be obtained with acids such as, for example, hydrochloric, phosphoric, acetic, lactic, tartaric or citric acid or alternatively with bases such as sodium hydroxide, potassium hydroxide, ammonia, lime, magnesia, alkanolamines such as triethanolamine, triisopropanolamine, aminomethylpropanol, or aminomethylpropanediol, or with amino acids and more particularly amino acids of a base nature such as lysine or arginine.

The compounds according to the invention are prepared, according to a process developed by the applicants, by acylating the chitosan by means of a saturated or unsaturated anhydride of the formula ##STR3## wherein R₁ has the meaning given above and wherein when n is equal to O, R'₂, R'₃ and R'₄ each independently represent hydrogen, methyl or acetoxy with the proviso that at least one of these radicals is hydrogen and radicals R'₂ and R'₃ can further form together a methylene residue; and wherein when n is equal to 1, R'₂, R'₃ and R'₄ each represent hydrogen, after which, in the case where an unsaturated anhydride is used, the product obtained can be subjected to an addition reaction with at least a primary or secondary amine whose hydrocarbon residue can be interrupted by one or more nitrogen atoms and/or substituted by one or more amine, hydroxyl, carboxyl, sulfonic or mercapto residues.

The chitosan acylation reaction is performed by adding to an aqueous solution of a chitosan salt, having a concentration of 1 to 20 weight percent thereof, alternately and by fractions, on the one hand, a base diluted solution intended to release amine functions of the chitosan and to salify the acid formed, and, on the other hand, the anhydride defined above. The reaction is performed between 10° and 50° C and preferably between 15° and 30° C, by using 0.3 to 2 moles of a saturated anhydride per equivalent of amine present in the chitosan, or 1 to 2 moles of unsaturated anhydride per equivalent of amine present in the chitosan. The anhydride can be used in this reaction either in powder form or in the form of a solution in an inert solvent such as, for example, dioxane, tetrahydrofuran or ethyl acetate.

Since the addition of the base causes partial precipitation of the chitosan, this reaction is performed in a heterogeneous medium. Further, since the anhydrides are unstable compounds in water, they can hydrolyze into the corresponding diacids, giving rise to a secondary reaction. However, despite these unfavorable conditions, the rate of acylation, computed from the acid number corresponding to this secondary reaction, is generally greater than 70%.

The chitosan salts used in this acylation reaction are, for example, the hydrochloride or acetate, while the bases can be sodium or potassium hydroxide, or again, and preferably, acid or neutral carbonates of sodium or potassium.

The saturated anhydrides used can be, for example, succinic anhydride, acetoxy succinic anhydride, methylsuccinic anhydride, diacetyl tartaric anhydride or diglycolic anhydride. The unsaturated anhydrides used can be, for example, maleic anhydride, itaconic anhydride or citraconic anhydride.

In the case where the starting anhydride is unsaturated, this acylation reaction can be followed by an addition reaction which makes it possible to achieve a range of quite varied products.

The addition reactions according to the invention can for the most part be performed at a pH above 7 and at a temperature between 20° and 60° C for several hours. Advantageously the reaction is carried out in a nitrogen atmosphere.

The amino reagents, used in these reactions, are present in a proportion of 0.1 to 10 moles per unsaturated pattern, this proportion being a function of the properties desired. Thus, for example, in the case of polyfunctional reagents it is possible to obtain, as a function of this number of moles, mobile, clear solutions, gels or compounds that are no longer soluble in water because of too great a reticulation.

The reagents used in the addition reactions according to the invention can be ammonia; mono- or polyamines such as methylamine, ethylamine, propylamine, butylamine, hexylamine, octylamine, dimethylamine, diethylamine, ethylenediamine, hexamethylenediamine, diethylenetriamine, triethylenetetramine and tetraethylenepentamine; alkanolamines such as monoethanolamine, isopropanolamine and diethanolamine; mercapto-amines such as β-mercapto ethylamine; amines with acid functions such as glycocoll, alanine, leucine, isoleucine, valine, aspartic acid, glutamic acid, serine, lysine, cysteine, methionine, cysteic acid, penicillamine, and methyltaurine; or again more complex compounds comprising polypeptidic linkings as glutathion and protein hydrolyzates. When a mercapto-amine is used, the addition on the double bond can also be made by the amine group or mercapto group.

For the preparation of the compounds according to the invention, it is desirable to use chitosan comprising from 70 to 95% of free amine groups. The percentage of these amine groups can be determined, in a known way, by dissolving of a sample in a known and excessive amount of hydrochloric acid which is determined back by a soda solution.

The chitosan that can be used for the purposes of the invention can also be selected as a function of the viscosity of their solutions. The viscosity of their solutions at 2% in 3% acetic acid, measured at 25° C after 24 hour can vary from 3 to 130 centipoises.

All the compounds obtained according to the process of the invention can be precipitated from their aqueous solution by modification of the pH and/or by addition of a solvent such as alcohol or acetone. Further, they can be isolated by other processes such as dialysis or passage over an ion exchange resin.

The compounds according to the invention are soluble in alkaline medium. They precipitate for the most part between pH 4 and pH 6; some of them are soluble in an excess of acid.

The compounds according to the invention constitute polyampholytes which present particularly advantageous properties in regard to filmogens and sequestrants of heavy metal ions.

Actually, the compounds of the invention present a particularly marked sequestering action with regard to ions of heavy metals, such as iron and copper, and in particularly slight concentrations. These ions, which generally come from water intake pipes, are particularly bothersome in certain industrial sections because they given rise to the formation of precipitates and they accelerate oxidation reactions. Thus, their elimination is particularly desirable.

Further, the compounds according to the invention remain in solution in the presence of alkaline earth ions, which advantageously differentiates them from natural polymers, such as alginates, which precipitate in an aqueous solution in the presence of these ions.

The combination of these two properties permits the compounds of the present invention to find a particularly interesting application as sequestrants of heavy metal ions in the food, pharmaceutical and textile industries. Their sequestering property in the presence of alkaline earth ions also makes it possible to use them in detergent compositions. Their ampholyte character makes it possible to associate them indifferently with cationic, anionic and, of course, non-ionic detergents. In these applications, they present, in relation to usual sequestrants such as EDTA, the advantage of being able to be used in clearly smaller proportions.

The compounds according to the invention further have filmogen properties. Actually, they give, on evaporation of their aqueous solution, perfectly transparent films, which are relatively hard and not sticky, and which can be plastic or brittle, depending on the particular compound selected. Further, the films are capable of exchanging water vapor with the surrounding environment without losing their film characteristics.

This property, joined to the characteristic, which most of the compounds according to the invention present, of precipitating from their aqueous solutions at a pH between pH 4 and pH 6, i.e., in the pH zone of the skin, has a very interesting application in cosmetic or pharmaceutical preparations intended to moisten the skin or give it natural constituents.

The present invention also relates to cosmetic compositions comprising an aqueous solution of at least one of the compounds according to the present invention in amounts of 0.1 to 20% by weight and preferably from 0.25 to 10% by weight.

The cosmetic compositions of this invention also contain, besides the novel chitosan derivatives, thickening or agglutinating agents such as carboxyvinyl polymers marketed by the Goodrich Chemical Company under the tradename Carbopol, softening agents such as lanolin, fatty acid esters known in cosmetology such as glycerin monostearate, Pur Cellin oil, preservatives, perfumes and the like.

These cosmetic compositions can be in the form of creams, lotions, gels, as well as in the form of oils or aerosols.

The novel chitosan derivatives of this invention can be used in the preparation of bath products and deodorants.

The following examples are given to illustrate the present invention.

EXAMPLE A Preparation of the product of condensation of chitosan with maleic anhydride (compound No. 10).

To 20 g of chitosan, having a viscosity of 3.5 cps (96 milliequivalents in amine groups), dispersed in 200 ml of water, there are added 8 ml of concentrated hydrochloric acid to neutralize exactly the free amine functions, with stirring to complete dissolving. If necessary, the undissolved chitosan particles can be filtered therefrom.

Then there are added at room temperature, alternately and in four equal fractions, on the one hand, 164 g (192 meq) of a sodium bicarbonate solution at 1.16 meq/g, and, on the other hand, 9.4 g (96 millimoles) of maleic anhydride powder. Addition of each fraction takes 5 to 10 minutes, the interval of introduction between two fractions being 30 to 45 minutes.

When the reaction is completed, the acid number is measured and is determined to be 0.03 meq/g, which corresponds to a total acidity of 12.5 meq.

The amount of base introduced is the stoichiometric amount necessary to neutralize both the hydrochloric acid used to make the chitosan salt and the maleamic acid formed.

The total acidity therefore takes into account the secondary reaction of hydrolysis. The rate of reaction is 12.5 × 100/96 = 13%, and consequently the rate of condensation of maleic anhydride on chitosan is 87%.

The compound thus prepared is isolated in acid form by adding 190 ml of normal hydrochloric acid. The resulting precipitate is filtered, drained, washed first with water and then with acetone, and dried.

The perfectly dry product can be ground and is in the form of a very slightly tinted white powder.

Other compounds are prepared according to the same mode of operation. The starting products and reaction conditions are given in Table I below.

                                      TABLE I                                      __________________________________________________________________________                                 Preci-                                                    Conc.     Molar  Reac-                                                                              pita-                                                     of  Conden-                                                                              pro-   tion                                                                               tion Com-                                          Polymer                                                                               poly-                                                                              sation                                                                               por-                                                                               Temp                                                                              time                                                                               Sol- pound                                         reactant                                                                              mer reactant                                                                             tions                                                                              ° C.                                                                       (hrs)                                                                              vent No.                                           __________________________________________________________________________     Chitosan   maleic           water                                              (3.5 cps)                                                                             5%  anhydride                                                                            1   20 3-4 (HCl)                                                                               10                                            Chitosan   maleic           water                                              (33 cps)                                                                              3.5%                                                                               anhydride                                                                            1   20 3-4 (HCl)                                                                               20                                            Chitosan   maleic           water                                              (117 cps)                                                                             2%  anhydride                                                                            1   20 3-4 (HCl)                                                                               30                                            Chitosan   itaconic         ethyl                                              (3.5 cps)                                                                             5%  anhydride                                                                            1   20 3-4 alcohol                                                                             40                                            Chitosan   itaconic                                                            (33 cps)                                                                              3.5%                                                                               anhydride                                                                            1   20 3-4  --  50                                            Chitosan   itaconic         ethyl                                              (117 cps)                                                                             2%  anhydride                                                                            1   20 3-4 alcohol                                                                             60                                            Chitosan   succinic                                                            (3.5 cps)                                                                             5%  anhydride                                                                            0.5 20 3-4      70                                            Chitosan   succinic         ethyl                                              (117 cps)                                                                             2%  anhydride                                                                            1   20 3-4 alcohol                                                                             90                                            Chitosan   succinic         water                                              (3.5 cps)                                                                             4.5%                                                                               anhydride                                                                            1   25 8   (HCl)                                                                               70 bis                                        Chitosan   succinic         water                                              (33 cps)                                                                              4.5%                                                                               anhydride                                                                            0.5 25 8   (HCl)                                                                               80                                            Chitosan   succinic         water                                              (33 cps)                                                                              3.5%                                                                               anhydride                                                                            1   25 8   (HCl)                                                                               80 bis                                        Chitosan   citraconic                                                          (3.5 cps)                                                                             4.5%                                                                               anhydride                                                                            1.2 25 8    --  100                                           __________________________________________________________________________

EXAMPLE B Preparation of the product of addition of compound No. 10 prepared in Example 1 with glycocoll.

There are dispersed 7 g of compound No. 10, or 20 meq, in 40 ml of water. Then 10 ml of 2N soda are added to neutralize and solubilize it. To the solution thus obtained there are added 1.5 g of glycocoll (20 meq) dissolved in 10 ml of 2N soda. The reaction mixture is then heated at 50° C for 1 hour, under a nitrogen atmosphere.

The compound thus obtained is soluble in an alkaline medium and an acid medium. It can be preserved in aqueous solution or isolated, by precipitation, either in the form of sodium salt by addition of ethyl alcohol, or at the isoelectric point by addition of hydrochloric acid, in an aqueous or dilute alcohol medium.

Other compounds, listed in Table II below, are prepared by the same mode of operation.

                                      TABLE II                                     __________________________________________________________________________                                 Preci-                                                  Conc.     Molar    Reac-                                                                              pita-                                                   of        pro-     tion                                                                               tion Com-                                          Polymer                                                                             poly-                                                                              Addition                                                                             por-                                                                               Temp time                                                                               Sol- pound                                         reactant                                                                            mer reactant                                                                             tions                                                                              ° C.                                                                         (hrs)                                                                              vent No.                                           __________________________________________________________________________              Ethanol-                                                              10   12% amine 1.2 60   5   Ethanol                                                                             11                                            10   10% Glycocoll                                                                            1   50   1   --   12                                            10   7%  Cysteine                                                                             1   20   1   Ethanol                                                                             13                                                     Methio-                                                               10   10% nine  1   60-90                                                                               10  --   14                                                     Methyl                                                                10   8%  taurine                                                                              1   50-70                                                                               9   --   15                                            20   10% Ammonia                                                                              3   50   120 --   21                                                     Methyl-                                                               20   12% amine 3   20   24  --   22                                                     Dimethyl-                                                             20   10% amine 1   20   20  --   23                                                     Diethanol-                                                            20   5%  amine 1   60   60  --   24                                            20   10% Glycocoll                                                                            1   60   21  --   25                                                     Aspartic                                                              20   15% acid  1   80   36  --   26                                            20   10% Cysteine                                                                             1   20   72  --   27                                                     Ethylene-                                                             40   8%  diamine                                                                              0.14                                                                               90   3   Acetone                                                                             41                                            40   8%  Sarcosine                                                                            10  35   24  Ethanol                                                                             42                                            40   5%  Serine                                                                               1.5 60   20  Ethanol                                                                             43                                            40   5%  Cysteine                                                                             1   50   5   --   44                                                     Glutamic           Water                                              10   18% acid  1   55-60                                                                               10  (HCl)                                                                               16                                                     Aspartic           Water                                              10   10% acid  1   25   10  (HCl) +                                                                             17                                                                        Ethanol                                            10   12% Leucine                                                                              1   25   24  Ethanol                                                                             18                                            10   4%  Tyrosine                                                                             1   80-85                                                                               5        19                                                     Trypto-                                                               10   10% phane 1   25   70  Ethanol                                                                             11 A                                                   Gluta-                                                                10   4.5%                                                                               thion*                                                                               1.2 25   24  Ethanol                                                                             12 A                                                   Penicill-                                                             10   5%  amine**                                                                              1.1 25   72  Ethanol                                                                             13 A                                          __________________________________________________________________________       *For condensation, only one acidity of the two of the Glutathion is           neutralized.                                                                    **The Penicillamine is solubilized in acid form in water and is reacted       in this form.                                                            

The following examples illustrate embodiments of cosmetic compositions containing the compounds of the present invention.

EXAMPLE 1

A softening cleansing milk is prepared having the following composition in % by weight:

    ______________________________________                                         Polyoxyethylene stearate  3.0                                                  Glycerin monostearate (Arlacel 165)                                                                      3.0                                                  Vaseline oil              36.2                                                 Self emulsifiable Pur Cellin oil                                                                         2.0                                                  Lanolin                   2.0                                                  Carboxyvinyl polymers (Carbopol 941)                                                                     0.1                                                  Triethanolamine           0.13                                                 Compound No. 70 bis       0.6                                                  Rose water                3.0                                                  Preservative (methyl p-hydroxybenzoate)                                                                  0.3                                                  Perfume                   0.2                                                  Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

The fatty components (polyoxyethylene stearate, glycerin monostearate, vaseline oil, Pur Cellin oil and lanolin) are melted. This mixture is then added to a solution of Carbopol 941 obtained by dissolving the Carbopol in one part of water and then neutralizing it with triethanolamine. An emulsion of the above components is then formed by stirring well.

Compound No. 70 bis is carefully dispersed in the rest of the water and neutralized by triethanolamine. Then the rose water, in which the preservative is dissolved, is added.

Finally, the preceding emulsion is diluted with the solution obtained with compound No. 70 bis and the whole is perfumed.

When applied to the skin, this milk gives an impression of freshness and softness.

EXAMPLE 2

A hydrating and protective cleansing base is prepared according to the same mode of operation as for the milk of Example 1, said base having the following composition in % by weight:

    ______________________________________                                         Stearic acid              2.0                                                  2,6,10,15,19,23-hexamethyltetracosane                                           (perhydrosqualene) C.sub.30 H.sub.62                                                                    20.0                                                 Glycerin monostearate (Arlacel 165)                                                                      2.0                                                  Triethanolamine           1.0                                                  Methyl parahydroxybenzoate                                                                               0.3                                                  Carboxyvinyl polymers (Carbopol 941)                                                                     0.3                                                  Triethanolamine           0.3                                                  Compound No. 70 bis       1.0                                                  Perfume                   0.3                                                  Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

This base has a good spreading power and assures a good protection to the skin.

EXAMPLE 3

According to the same mode of operation as for the milk of Example 1, there is prepared a softening cream for legs that have undergone depilation, said cream having the composition by weight in % of:

    ______________________________________                                         Fatty acid ester (Pur Cellin oil)                                                                        2.0                                                  Vaseline oil              7.0                                                  Isopropyl myristate       1.5                                                  2,6,10,15,19,23-hexamethyltetracosane                                           (perhydrosqualene C.sub.30 H.sub.62                                                                     3.5                                                  Lanolin Alcohols (Amerchol L 101)                                                                        0.3                                                  Stearic acid              1.4                                                  Glycerin monostearate     2.0                                                  Hexadecylic alcohol       1.0                                                  Pure cetyl alcohol        0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Carboxyvinyl polymers (Carbopol 941)                                                                     0.25                                                 Triethanolamine           0.25                                                 Perfume                   0.2                                                  Triethanolamine           0.7                                                  Compound No. 10           2.5                                                  Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

When applied to the skin, this cream gives it an impression of softness.

EXAMPLE 4

According to the same mode of operation as for the milk of Example 1, a hand cream is prepared with the composition in % by weight:

    ______________________________________                                         Paraffin oil              20.0                                                 Stearic acid              6.0                                                  Triethanolamine           3.0                                                  Glycerol monostearate     2.0                                                  Soybean lecithin          1.0                                                  Compound No. 10           3.0                                                  Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

This cream is very penetrating and imparts good suppleness to the skin shortly after its application thereto.

EXAMPLE 5 Preparation of an after-shave gel.

This gel having the following composition in % by weight:

    ______________________________________                                         Compound No. 80           0.25                                                 Carbopol 934              0.25                                                 Triethanolamine           0.375                                                Propylene glycol          5.0                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Perfume                   0.2                                                  Water, sufficient for     100%                                                 ______________________________________                                    

is prepared as follows:

A solution of compound No. 80 obtained by dispersing said compound in one part of water and neutralized with triethanolamine is mixed with Carbopol 934 neutralized with triethanolamine in propylene glycol. The preservative dissolved in water is then added to the whole. Perfume is then added to the resulting mixture.

This gel, when applied to the skin, gives it a feeling of freshness.

EXAMPLE 6 Preparation of a body cream with the composition in % by weight:

    ______________________________________                                         Vaseline oil              9.5                                                  Oleyl alcohol             1.0                                                  Glycerol monostearate     1.0                                                  Stearic acid              1.0                                                  Carboxyvinyl polymers (Carbopol 941)                                                                     0.15                                                 Triethanolamine           0.65                                                 Propylene glycol          2.0                                                  Preservative              0.3                                                  Compound No. 10           0.4                                                  Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

The fatty components and the preservative are mixed and this phase is poured into the Carbopol gel containing one part water, triethanolamine and propylene glycol. It is then emulsified for 10 minutes.

The cream thus obtained is diluted with a solution of compound No. 10 neutralized with triethanolamine, in 30 ml of demineralized water. It is finally cooled to 25° C. This cream spreads very easily and gives the skin a feeling of softness.

EXAMPLE 7 Preparation of a hydrating lotion.

This lotion having the following composition in % by weight:

    ______________________________________                                         Hamamelis water           50.0                                                 Compound No. 80           1.0                                                  Aminomethylpropanol       0.3                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Perfume                   0.2                                                  Water, sufficient for     100%                                                 ______________________________________                                    

is prepared as follows:

The preservative is dissolved in water. Compound No. 80 is dispersed in one part of water and aminomethylpropanol is dissolved in the remaining water. The resulting three solutions are mixed and neutralized with aminomethylpropanol. The hamamelis water and perfume are then added. This lotion, when applied to the skin, gives it a feeling of freshness.

EXAMPLE 8 Preparation of a protective beauty cream.

    ______________________________________                                         Composition in % by weight:                                                    Paraffin oil              15.0                                                 Stearic acid              5.0                                                  Triethanolamine           2.5                                                  Cetyl alcohol             3.0                                                  Compound No. 10           2.0                                                  Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

EXAMPLE 9

A perfumed bath oil of the composition in % by weight is prepared:

    ______________________________________                                         Propylene glycol          8.0                                                  Isopropyl myristate       1.0                                                  Compound No. 70 bis       10.2                                                 Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

Compound No. 70 bis is dissolved in water, after neutralization with aminomethylpropanol, then the other ingredients of the formula are added.

EXAMPLE 10

A bath cream of the composition in % by weight is prepared:

    ______________________________________                                         Paraffin oil              40.0                                                 Cetyl stearyl alcohol     3.0                                                  Sorbitan monostearate     3.0                                                  Polyoxyethylene sorbitan monolaurate                                                                     4.0                                                  Compound No. 70 bis       4.0                                                  Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

The novel chitosan derivatives can also enter into the composition of filmogeneous products such as preparations for coloring the skin, deodorizing products and anti-spot products.

As examples there can be cited:

EXAMPLE 11

A filmogeneous product of the composition in % by weight is prepared:

    ______________________________________                                         Compound No. 70 bis       3                                                    Triethanolamine or base amino acids,                                            sufficient amount for    pH 7                                                 Propylene glycol          6                                                    Titanium dioxide          8                                                    Pigments                  0.1                                                  Carboxymethyl cysteine    1                                                    Hexachlorophene           0.1                                                  Propyl-p-hydroxybenzoate  0.3                                                  Sterile demineralized water, sufficient                                         for                      100%                                                 ______________________________________                                    

This product is used in skin care.

EXAMPLE 12 Preparation of deodorants for private hygiene in the form of an aerosol foam

    ______________________________________                                         Compound No. 10           3                                                    Triethanolamine or base amino acids,                                            sufficient for           pH 7                                                 Lauryl sulfate            30                                                   Lanolin                   2                                                    Hypoallergenic perfume    0.2                                                  Sterile water, sufficient for                                                                            100%                                                 ______________________________________                                    

To 90 parts of the above mixture there are used 10 parts of the following aerosol propellant in a 50/50 mixture: Freon 114 (CClF₂ CClF₂)/Freon 12 (CCl₂ F₂).

EXAMPLE 13

Protective lotion:

The following composition is prepared in % by weight:

    ______________________________________                                         Compound No. 70 bis       0.5                                                  Triethanolamine or base amino acids,                                            sufficient for           pH 7                                                 Propylene glycol          30                                                   Sterile water, sufficient for                                                                            100%                                                 ______________________________________                                    

EXAMPLE 14

According to the method for preparing the milk of Example 1, a protective day cream having the composition in % by weight is prepared:

    ______________________________________                                         Stearic acid              2.00                                                 Cosbiol                   20.00                                                Glycerol monostearate     2.00                                                 Triethanolamine           1.00                                                 Preservative (methyl-p-hydroxybenzoate)                                                                  0.30                                                 Carbopol 941              0.30                                                 Compound 11 A             1.00                                                 Perfume                   0.30                                                 Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

This cream assures a good protection of the skin.

EXAMPLE 15

An after-shave fluid having the composition in % by weight is prepared as follows:

    ______________________________________                                         Compound No. 44           0.50                                                 Carbopol 934              0.25                                                 Triethanolamine           0.25                                                 Propylene glycol          5.00                                                 Preservative (methyl-p-hydroxybenzoate)                                                                  0.30                                                 Perfume                   0.2                                                  Sterile demineralized water, sufficient                                        for                       100%                                                 ______________________________________                                    

A solution of compound No. 44 obtained by dispersing said compound in one part of water and then neutralizing it with triethanolamine, is mixed with the propylene glycol. The preservative, dissolved in water, and then the perfume are added. This gel, when applied to the skin, gives the feeling of freshness.

EXAMPLE 16

A protective cream having the following composition in % by weight is prepared:

    ______________________________________                                         Paraffin oil              15.0                                                 Stearic acid              5.0                                                  Triethanolamine           2.5                                                  Cetyl alcohol             3.0                                                  Compound No. 18           2.0                                                  Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

EXAMPLE 17

A bath product having the following composition in % by weight is prepared as follows:

    ______________________________________                                         Propylene glycol          8.0                                                  Isopropyl myristate       1.0                                                  Compound No. 13 neutralized with                                                aminomethyl propanol     10.2                                                 Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

Compound No. 13 is dissolved in water after neutralization with aminomethylpropanol. Then the other above components are added thereto.

EXAMPLE 18

A bath cream having the following composition in % by weight is prepared as follows:

    ______________________________________                                         Paraffin oil              40.00                                                Mixture of fatty alcohols of C.sub.16 and                                       C.sub.18 (Lanette O)     3.00                                                 Sorbitan monostearate (Arlacel 60)                                                                       3.00                                                 Sorbitan monolaurate (Tween 20)                                                                          4.00                                                 Compound No. 42           4.00                                                 Perfume                   0.2                                                  Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Water, sufficient for     100%                                                 ______________________________________                                    

The fatty components are melted at 75° C. Compound No. 42 is dissolved in water with the preservative and the resulting solution is then heated to 75° C. The melted components and solution of compound 42 are mixed with stirring. After cooling, the perfume is incorporated.

EXAMPLE 19

According to the same method for preparing the milk of Example 1, a regenerating night cream having the following composition in % by weight is prepared:

    ______________________________________                                         Cetyl ether polyoxyethylene (10 moles)                                          (BRIJ 56)                2.00                                                 Stearyl ether polyoxyethylene (10 moles)                                        (BRIJ 76)                2.00                                                 Glycerin monostearate     4.00                                                 Perhydrosqualen (Cosbiol) 9.00                                                 Vaseline oil              32.00                                                Stearic acid              2.00                                                 Compound 70 bis           5.00                                                 Perfume                   0.30                                                 Preservative (methyl-p-hydroxybenzoate)                                                                  0.30                                                 Triethanolamine           0.10                                                 Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

EXAMPLE 20

A regenerating lotion having the following composition in % by weight is prepared as follows:

    ______________________________________                                         Compound No. 12 A         2.00                                                 Rose water                50.00                                                Preservative (methyl-p-hydroxybenzoate)                                                                  0.3                                                  Perfume                   0.2                                                  Sterile demineralized water, sufficient                                        for                       100%                                                 ______________________________________                                    

The preservative is dissolved in water, then compound No. 12 A is also dissolved. The rose water and perfume are introduced therein and the whole is filtered and dyed.

EXAMPLE 21

According to the method of preparing the milk of Example 1, a cleansing base having the following composition in % weight is prepared:

    ______________________________________                                         Stearic acid              2.00                                                 Vaseline oil              20.00                                                Glycerol monostearate     2.00                                                 Hexadecyl alcohol         0.50                                                 Cetyl alcohol             0.50                                                 Triethanolamine           1.30                                                 Preservative (methyl-p-hydroxybenzoate)                                                                  0.30                                                 Carbopol 941              0.30                                                 Compound No. 16           1.00                                                 Perfume                   0.30                                                 Demineralized water, sufficient for                                                                      100%                                                 ______________________________________                                    

In the above cosmetic compositions the following components employed are more precisely identified as follows:

    ______________________________________                                         Amerchol L 101                                                                            Liquid, multi-sterol, non-ionic,                                                 surface-active penetrant, emollient                                            and emulsifier. Sterols and higher                                             alcohols are present only in their                                             free forms. Anhydrous, oil soluble,                                            water dispersible, practically                                                 odorless, tasteless and pale straw                                             color.                                                                       Cosbiol                                                                         Perhydrosqualene.                                                             Carbopol 934                                                                    Carboxypolymethylene.                                                         Carbopol 941                                                                    a carboxyvinyl polymer                                                        Pur Cellin Oil                                                                  fatty acid ester with alkylated                                                 ramifications                                                     ______________________________________                                     

What is claimed is:
 1. A sequestering agent for ions of a heavy metal in an aqueous solution consisting essentially of a chitosan derivative consisting of randomly distributed patterns of the formulae: ##STR4## the proportions of these three patterns being, respectively, 5 to 30% for A, 5 to 40% for B and 30 to 90% for C, R representing a member selected from the group consisting of ##STR5## wherein R₁ represents a member selected from the group consisting of hydrogen and methyl, n is equal to (a) 0, in which case R₂, R₃ and R₄, each independently, represent a member selected from the group consisting of hydrogen, methyl, hydroxy, acetoxy, amino, monoalkylamino or dialkylamino wherein the alkyl moiety of each has 1-12 carbon atoms and wherein each is optionally interrupted by one or more nitrogen atoms or substituted by one or more amino, hydroxyl, mercapto, carboxyl, alkylthio wherein the alkyl moiety has 1 to 8 carbon atoms and sulfonic groups, alkylthio wherein the alkyl moiety has 1- 4 carbon atoms and carries an amino residue, and a residue of glutathion, at least one of R₂, R₃ and R₄ being hydrogen and radicals R₂ and R₃ being able to form together a methylene radical, and (b) 1, in which case R₂, R₃ and R₄ each represent hydrogen, and the salts formed by this derivative with a base selected from the group consisting of sodium hydroxide, potassium hydroxide, ammonia, lime, magnesia and alkanolamine and an acid selected from the group consisting of hydrochloric, phosphoric, acetic, lactic, tartaric and citric.
 2. The sequestering agent of claim 1 wherein said heavy metal is selected from the group consisting of iron and copper.
 3. The sequestering agent of claim 1 for ions of a heavy metal in lime or magnesium water.
 4. The sequestering agent of claim 1 for ions of a heavy metal in the presence of an anionic, cationic or nonionic detergent. 